title: Systemic therapies in hepatocellular carcinoma: present and future.
abstract: Hepatocellular carcinoma (HCC) is now the third leading cause of cancer deathsworldwide and is generally presented at an advanced stage, limiting patients' quality of life. The conventional cytotoxic systemic therapy has proved to be ineffective in HCC, since its induction several decades ago. Today it is possible to use our knowledge of molecular hepatocarcinogenesis to provide a targeted therapy. Sorafenib has demonstrated large improvements in overall survival in HCC. This review describes the molecular mechanisms and potential therapeutic targets, focusing on sorafenib, sunitinib, tivantinib, antiangiogenic agents, and current and future immunotherapies. Thus, it will be necessary in the future to classify HCCs into subgroups according to their genomic and proteomic profiling. The identification of key molecules/receptors/signaling pathways and the assessment of their relevance as potential targets will be the main future challenge potentially influencing response to therapy. Defining molecular targeted agents that are effective for a specific HCC subgroup will hopefully lead to personalized therapy.
authors.affiliation: Hepatology Unit - Department of Medical & Pediatric Science, University of Catania Policlinic, Via S Sofia 78, 95123, Catania, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bertino
authors.forename: Isidoro
authors.initials: I
authors.lastname: Di Carlo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ardiri
authors.forename: Giuseppe Stefano
authors.initials: GS
authors.lastname: Calvagno
authors.forename: Shirin
authors.initials: S
authors.lastname: Demma
authors.forename: Giulia
authors.initials: G
authors.lastname: Malaguarnera
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bertino
authors.forename: Mariano
authors.initials: M
authors.lastname: Malaguarnera
authors.forename: Adriana
authors.initials: A
authors.lastname: Toro
authors.forename: Michele
authors.initials: M
authors.lastname: Malaguarnera
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging